Scarcity of high-resolution structural data has impeded an understanding of the recognition and anti-aggregation mechanisms of molecular chaperones. We recently reported the first ever structures of molecular chaperones in complex with unfolded proteins. We used advanced NMR spectroscopy techniques and isotope labeling approaches to determine the solution structure of the 50 kDa Alkaline Phosphatase (PhoA) captured in the unfolded state by three molecules of the Trigger Factor (TF) chaperone (~50 kDa), forming a ~200 kDa complex in solution [1]. We determined the high-resolution structure of each one of the TF molecules in complex with the corresponding unfolded PhoA region and reported how a chaperone dynamically engages its substrate. Very recently, we reported the structure of SecB, a chaperone that exhibits strong antifolding activity, in complex with PhoA and maltose binding protein (MBP) captured in their unfolded states [2]. The structural data revealed a unique complex architecture that explains the activity on the chaperone. Taken together, the data show how the different architectures of chaperones result in distinct binding modes with client proteins that ultimately define the activity of the chaperone.